Osteoporosis is a condition characterized by a reduction in the bone mineral density, impaired bone quality and frequent occurrence of fractures resulting from minor trauma. Current assessment of osteoporotic fracture risk is based on bone densitometry techniques that do not entirely predict fracture risk or the impact of a particular intervention. Bone quality encompasses bone geometry and macro-architecture, trabecular bone structure, matrix calcification, bone turnover. The quantitative analysis of bone structure and the elucidation of relationships between structural parameters and bone strength may have a major impact upon the prediction of fracture risk and evaluation of different therapies. In this application, we are proposing to extend our previous work and make use of recent advances in hardware and software, to obtain three-dimensional (3-D) magnetic resonance (MR) images with resolutions of approximately 100x 100x300 microns so as to accurately quantify the 3-D architecture of the trabecular bone network in the radius, calcaneus and proximal femur, and perform a rigorous evaluation of the impact of these data on the pathophysiological changes in skeletal bone and trabecular micro-architecture in aging, osteoporosis and fracture susceptibility. The specific aims of this study will be to establish non-invasive, reproducible imaging surrogates that can be used to assess bone quality in vivo. MR image derived parameters of trabecular micro-architecture at the different measurement sites will be related to age, menopause status and osteoporotic status in a cohort of 250 subjects. The primary question that will be addressed is whether MR assessment of trabecular micro-architecture at the radius, calcaneus and proximal femur, combined with bone mineral density, provide a means to explain the discrepancy between bone mineral density and fracture occurrence. We will assess whether using MR derived measures of trabecular bone at the different skeletal sites show site specific differences, relationship between structure and bone mineral density at these sites, and whether these measures may be used to complement bone mineral density measurements in the study of osteoporosis.